The proposed experiments are designed to yield important new information on the physiological significance and in vivo function of Paneth cells. The lysozyme content of Paneth cells and their response to physiological stimuli will be investigated by the use of specific radioimmunoassay for lysozyme and also by ultrastructural immunocytochemistry. The effect of the presence or absence of the intestinal flora on the lysozyme content of Paneth cells and the adsorption of this enzyme to the enteric surface coat of the microvillus border will be characterized by using germfree rats, conventionalized rats, and rats having self-filling blind intestinal loops. Production of lysozyme by other intestinal epithelial (i.e., goblet cells) will be investigated in different regions of the gastrointestinal tract by use of ultrastructural immunocytochemistry. The heterophagic origin of lysosomes will be assessed by quantitatively examining the distribution of lysosomes in conventionalized rats and in germfree littermates in order to determine if there is a direct relationship between the presence of the intestinal flora and the phagolysosomal apparatus of the Paneth cells. Evaluation of the role Paneth cells play in the production of intestinal lysozyme and its interaction with microorganisms closely associated with the mucosal surface should provide a better understanding of the natural defense mechanisms of the gastrointestinal tract. In addition, information of this nature may help to elucidate the physiological significance of lysozyme in other external secretions of mucosal surfaces, such as tears (lacrimal gland), colostrum-milk (mammary gland), bronchial and upper respiratory secretions, and cervical mucus (uterus).